Routine monitoring of the joints from 452 SAIDS cases over a 6 year period indicates that 61% had reactive joint disease, consisting of synovial cell activation (23%) and mononuclear cell infiltration (27%) of the synovium. The hyperplastic synovial membrane usually immunostains for TNFa . Considering the association of synovial cell hyperplasia with diarrhea, the small and large intestines of the acute and chronic phases of SIV infection were evaluated using immunohistochemistry. Cells responsible for soluble intestinal immunity (IgA and IgG) change in cell output with disease. Disease mediators (TNFa and NO) and the presence or absence of SIV containing cells of the lamina propria were evaluated. Changes were more pronounced in the colonic lamina propria. In a vaccine trial, animals sacrificed at 3-weeks post-inoculation had a pronounced reduction in IgA and an increase in IgG staining cells in the lamina propria of both the small and large intestines. This supports the hypot hesis that the soluble immunity of the gut is compromised early in SIV infection. Cell patterns of the intestinal lamina propria show an early stimulation of CD4+ cells which then drops in the rapid progressors. The (( and(( T cells were increased in the colonic and ileal lamina propria of SIV infected animals. There was no change which indicated T cell activation in the early phase of intestinal SIV infection. Both TNF and NO were used as disease indicators. Both TNF( and NO (nitrotyrosine) were increased in the colonic and ileal lamina propria of SIV infected animals. The mononuclear cell infiltrate and syncytial cell inflammation are both changes associated with SIV infection. Both cellular changes are associated with the presence of SIV. It is clear that prominent changes in intestinal soluble immunity, cellular changes, and elevation of mediators are all associated with an early compromise in intestinal immunity. The response of synovial cell hyperplasia, as seen in ter minal SIV cases, most likely is a response to the "acute phase response" in SIV infected macaques. FUNDING PUBLICATIONS